Authors' objectives

To investigate the association between hormone replacement therapy (HRT) and colon cancer.

Searching

MEDLINE and Cancerlit were searched (dates not stated). Keywords included: colorectal neoplasm or colonic neoplasm or gastrointestinal neoplasm or rectal neoplasm, and oestrogen replacement therapy or estrogens or contraceptives, oral. Reference lists from the internet sites Cancernet and Oncolink and from published studies and a previous meta-analysis were searched (see Other Publications of Related Interest).

Only studies published in French or English up to December 1996 were included. Unpublished studies were excluded.

Study selection

Assessment of study quality

No formal validity assessment was conducted but a sensitivity analysis was conducted in which studies were grouped according to design, year of publication, and the degree of adjustment for confounding.

Data extraction

The author does not state how the data were extracted for the review, or how many of the reviewers performed the data extraction.

Methods of synthesis

Results of the review

Nineteen studies were included: 8 cohort studies (although one of these appears to be a randomised clinical trial) and 11 case-control studies.

Ever use versus never use of HRT (n=19 studies).

There was substantial heterogeneity across studies, this remained for subsets of studies defined by design, year of publication and adjustment for confounding (p ranged from greater than 0.001 for all studies to 0.36 for studies published before 1990). The summary RR obtained using a fixed-effect meta-analysis was 0.82 (0.76, 0.89) indicating a protective effect of the use of HRT on colorectal cancer. The summary RR from the random-effects model was 0.81 (95% CI: 0.70, 0.93). Summary measures of effect varied little across subgroups (fixed-effect RRs ranged from 0.76 for studies which controlled for confounding to 0.93 for studies published before 1990).

Current verus past use of HRT - n= 6 studies.

Studies of current use showed evidence of heterogeneity (p=0.07), studies of past use appeared to be fairly homogeneous (p=0.48). The summary estimate of the RR obtained for current use was 0.65 (95% CI: 0.54 to 0.79) this was less than that for past use (RR=0.78, 95% CI: 0.69, 0.88). Estimates for sub-groups within these categories (cohort studies only, case-control studies only and studies published after 1990) were similar to the overall estimates.

Long (greater than or equal to 5 years) versus short-term (greater than 5 years) use of HRT.

Both sub-sets of studies showed evidence of heterogeneity (p=0.04 for those of short-term use and p=0.02 for long-term use). The summary estimate of the RR obtained for short-term use was 0.84 (95% CI: 0.73, 0.97), this was greater than that for long-term use (RR=0.69, 95% CI: 0.58, 0.82). All RR estimates for the subgroup (cohort studies only, case-control studies only and studies published after 1990) analyses were greater for studies of short-term duration compared to those of long-term duration when the estimates for similar sub-groups were compared.

Authors' conclusions

The results suggest a small but significant protective effect of the use of HRT on colon cancer. The finding of a dose-response with a greater effect for longer duration of treatment is consistent with this finding.

CRD commentary

A reasonable review of the area. The literature search could have been improved by searching further databases and including unpublished studies and those published in languages other than English and French, limiting the search on these factors may have resulted in some important studies being missed. No details were provided on the participants included in the review limiting the applicability of results. No formal validity assessment was carried out, however some methodological features of the studies were investigated in the sensitivity analysis (study design and control of confounding). Study details and results of the analysis were clearly presented. In view of the substantial heterogeneity between studies included in the main review a meta-analysis should not have been attempted. Instead a meta-regression, in which possible sources of heterogeneity are controlled for, or a qualitative analysis should have been presented. In view of these limitations, not a great deal of confidence can be placed in the author's conclusions.

Implications of the review for practice and research

The author stated that women are unlikely to start HRT to reduce their risk of colon cancer, but establishing this chemo-preventive property of menopausal hormones could help put into perspective the small increase in breast cancer risk reported in many studies as well as other important health outcomes, such as cardiovascular disease, osteoporosis, and quality of life, in the decision to use or not use these products. Additional studies are needed to estimate summary effects with more precision to better discriminate between categories of users, and to establish a causal relationship.

Bibliographic details

Hebert-Croteau N. A meta-analysis of hormone replacement therapy and colon cancer in women. Cancer Epidemiology, Biomarkers and Prevention 1998; 7(8): 653-659. [PubMed: 9718216]

Other publications of related interest

1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. 2. MacLennan SC, MacLennan AH, Ryan P. Colorectal cancer and oestrogen replacement therapy. A meta-analysis of epidemiologic studies. Medical Journal of Australia 1995;162:491-3.

Indexing Status

Subject indexing assigned by NLM

MeSH

Adult; Age Distribution; Aged; Canada /epidemiology; Case-Control Studies; Cohort Studies; Colonic Neoplasms /epidemiology /prevention & control; Confidence Intervals; Estrogen Replacement Therapy /statistics & numerical data; Female; Incidence; Middle Aged; Randomized Controlled Trials as Topic; Risk Factors

AccessionNumber

11998001427

Database entry date

31/07/2000

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.